Acute Effects of Early Life Stress on Pain and the Neonatal Dorsal Root Ganglion

Early life stress (ELS) can have lasting effects on pain perception. Newborn infants in the neonatal intensive care unit experience various stressors, ranging from maternal separation to skin-breaking procedures. Preclinical studies demonstrated that ELS sensitizes nociceptive circuits within the mature nervous system, leading to exacerbated pain responses in adulthood. However, the acute effects of ELS on nociceptive processing in the immature nervous system remain poorly understood. As a result, here we investigated the effects of ELS on pain and the transcriptional profile of sensory neurons in neonatal mice. Neonatal limited bedding between postnatal days (P)2 and P9 was used to model early life chronic stress, with control litters housed under normal bedding conditions. Our behavioral results show increased sensitivity to noxious cold, mechanical pressure, and tactile stimuli in ELS pups compared to the control group at P9-P12. Bulk RNA-seq analysis of P9 lumbar dorsal root ganglia (DRG) after ELS revealed a >16-fold reduction in mRNA expression of the genes encoding the neuropeptides somatostatin (Sst) and natriuretic polypeptide b (Nppb), which are known to be highly co-localized in a subpopulation of DRG neurons implicated in chronic pain and itch. In situ hybridization confirmed that neonatal DRG neurons expressed significantly lower mRNA levels of both Sst and Nppb in pups exposed to ELS. Collectively, these results suggest that ELS elicits short-term changes in nociceptive processing within developing mice. These findings represent a critical first step in unraveling the molecular mechanisms governing the interaction between chronic stress and pediatric pain. NS080889 to MLB.